A novel approach to the understanding of the antitumor activity of lactones and epoxides is proposed which involves identification and optimization of each of the several individual parameters which influence biological activity. First, we plan to clearly establish the influence of strain, neighboring groups, and electronic effects on the chemical reactivity of lactones and epoxides. The relationship between chemical reactivity, intrinsic activity, and antitumor activity will then be studied using in vivo and "cell free" test systems. These studies should elucidate the other factors (e.g. transport, metabolic activation, etc.) which influence the biological activity of these compounds. Concurrently, we have designed and plan to prepare several mixed polyfunctional lactones and epoxides as potential tumor inhibitors. A study of these compounds will, in addition, also lead to a better understanding of the relationship of structure to chemical reactivity and antitumor activity. We feel that this approach will serve as a model for the determination of the relationship between chemical reactivity and biological activity for other agents, including carcinogens and penicillins. BIBLIOGRAPHIC REFERENCES: I.K. Stamos, G.A. Howie, P.E. Manni, W.J. Haws, S.R. Byrn, and J.M. Cassady, Synthesis and Structures of Dilactones Related to Anemonin, J. Org. Chem., 42, 1703-1709 (1977). J.M. Cassaday, G.A. Howie, J.M. Robinson, and I.K. Stamos, Methyl alpha-(Bromomethyl) Acrylate, Organic Synthesis, (1977).